Biomedical subjects
Publications and source records attributed to G Deneffe.
We describe a 58-year-old male diagnosed with a tumour of the left lung, which on subsequent thoracotomy proved to be invading the phrenic nerve. The clinical and spirometric outcome of a lobectomy, which resulted in a postoperative ipsilateral hemidiaphragmatic paralysis, versus the alternative surgical option of a pneumonectomy is discussed.
OBJECTIVE: Modern large single institutional reports on pulmonary sequestration (PS) are extremely rare. We were interested in comparing patients with PS referred by our pediatric versus adult pulmonologists. METHODS: Hospital notes of all patients operated on between 1978 and 1997 for a congenital broncho-pulmonary malformation were reviewed. In 28 patients, the parenchymal lesion was vascularized by a systemic artery and was separated from the bronchial tree, thus matching the strict definition of PS. Patient characteristics and outcome were analyzed comparing the pediatric group (< or =16 years: n=13; mean age, 3+/-5 years) versus the adult group (>16 years: n=15; mean age, 33+/-13 years). RESULTS: No significant differences between both groups were observed in sex, side, type of sequestration, pulmonary venous drainage, associated anomalies, hospital and late outcome, and patient's overall score. Patients (n=21) with the intralobar type of sequestration presented significantly more often with an infection when compared with patients (n=7) with the extralobar type (91 versus 14%; P=0.0033). When compared with the pediatric group, patients in the adult group had significantly more respiratory infections (87 versus 38%; P=0.016), and also required a lobectomy more often (67 versus 31%; P=0.056). CONCLUSIONS: The extralobar type of sequestration often remains asymptomatic, and is usually an incidental finding during infancy. The intralobar type mostly presents with recurrent infections in adulthood resulting in more lobectomies. We believe these findings support our current policy to remove any pulmonary malformation whenever diagnosed in order to: (1), prevent infection and other potentially serious late complications which may compromise the surgical outcome; and (2), enhance the chance of a parenchymal-sparing resection.
OBJECTIVE: To assess the value of positron emission tomography with 18fluorodeoxyglucose (FDG-PET) for preoperative lymph node staging of patients with primary cancer of the esophagus and gastroesophageal junction. SUMMARY BACKGROUND DATA: FDG-PET appears to be a promising tool in the preoperative staging of cancer of the esophagus and gastroesophageal junction. Recent reports indicate a higher sensitivity and specificity for detection of stage IV disease and a higher specificity for diagnosis of lymph node involvement compared with the standard use of computed tomography and endoscopic ultrasound. METHODS: Forty-two patients entered the prospective study. All underwent attenuation-corrected FDG-PET imaging of the neck, thorax, and upper abdomen, a spiral computed tomography scan, and an endoscopic ultrasound. The gold standard consisted exclusively of the histology of sampled nodes obtained by extensive two-field or three-field lymphadenectomies (n = 39) or from guided biopsies of suspicious distant nodes indicated by imaging (n = 3). RESULTS: The FDG-PET scan had lower accuracy for the diagnosis of locoregional nodes (N1-2) than combined computed tomography and endoscopic ultrasound (48% vs. 69%) because of a significant lack of sensitivity (22% vs. 83%). The accuracy for distant nodal metastasis (M+Ly), however, was significantly higher for FDG-PET than the combined use of computed tomography and endoscopic ultrasound (86% vs. 62%). Sensitivity was not significantly different, but specificity was greater (90% vs. 69%). The FDG-PET scan correctly upstaged five patients (12%) from N1-2 stage to M+Ly stage. One patient was falsely downstaged by FDG-PET scanning. CONCLUSIONS: FDG-PET scanning improves the clinical staging of lymph node involvement based on the increased detection of distant nodal metastases and on the superior specificity compared with conventional imaging modalities.
OBJECTIVE: To investigate the additional effect of incentive spirometry to chest physiotherapy to prevent postoperative pulmonary complications after thoracic surgery for lung and esophageal resections. DESIGN: Randomized controlled trial. SETTING: University hospital, intensive care unit, and surgical department. PATIENTS: Sixty-seven patients (age, 59 +/- 13 yrs; forced expiratory volume in 1 sec, 93% +/- 22% predicted) undergoing elective thoracic surgery for lung (n = 40) or esophagus (n = 27) resection. INTERVENTIONS: Physiotherapy (breathing exercises, huffing, and coughing) (PT) plus incentive spirometry (IS) was compared with PT alone. MEASUREMENTS AND MAIN RESULTS: Lung function, body temperature, chest radiograph, white blood cell count, and number of hospital and intensive care unit days were all measured. Pulmonary function was significantly reduced after surgery (55% of the initial value) and improved significantly in the postoperative period in both groups. However, no differences were observed in the recovery of pulmonary function between the groups. The overall score of the chest radiograph, based on the presence of atelectasis, was similar in both treatment groups. Eight patients (12%) (three patients with lobectomy and five with esophagus resection) developed a pulmonary complication (abnormal chest radiograph, elevated body temperature and white blood cell count), four in each treatment group. Adding IS to regular PT did not reduce hospital or intensive care unit stay. CONCLUSIONS: Pulmonary complications after lung and esophagus surgery were relatively low. The addition of IS to PT did not further reduce pulmonary complications or hospital stay. Although we cannot rule out beneficial effects in a subgroup of high-risk patients, routine use of IS after thoracic surgery seems to be ineffective.
Congenital lung malformations, primary and secondary, contribute to an important portion of pediatric thoracic surgery. One purpose of this report is to outline the close relation in terms of embryology and clinical presentation of congenital parenchymatous pulmonary malformations. In a retrospective study we also aim to evaluate our experience with the diagnosis and surgical management of congenital parenchymatous bronchopulmonary malformations and to compare our data with the literature. From January 1979 to December 1996 a series of 48 patients, 30 males (62.5%) and 18 females (37.5%), were operated on for congenital bronchopulmonary malformations. Pulmonary sequestration, bronchogenic cysts, congenital lobar emphysema, and congenital cystic adenomatoid malformation were seen in 16, 13, 5, and 14 patients, respectively. The first clinical symptoms occurred at a mean age of 8.8 years (1 day to 62 years), and the mean age at the time of surgical intervention was 9.3 years (1 day to 62 years). The maximum time between first symptoms and surgical treatment was 27 years. A lobectomy was performed in 22 cases; in the other patients more lung-preserving surgery such as enucleation or sequestrectomy was performed. Only one postoperative death occurred following lobectomy for pulmonary sequestration, and it was due to pulmonary hypoplasia and pulmonary hypertension. Eleven other patients presented with postsurgical complications: pneumothorax (n = 5), pleural effusion (n = 3), prolonged air leak (n = 2), portal vein thrombosis (n = 1), and hemorrhage requiring reintervention (n = 1). We conclude that any thoracic cystic lesion expanding on chest radiography should be an indication for surgical resection, even if asymptomatic, because of the risk of pulmonary compression, infection, or malignant degeneration. In the few cases of a fetal intrathoracic mass, prenatal diagnosis and intrauterine intervention may be indicated, and these indications are also discussed.
OBJECTIVE: Data from the literature indicate that chemotherapy prior to resection may improve the results. However, only few and conflicting data are reported regarding the correlation between downstaging of mediastinal nodes and outcome. The aim of this study was to look at the correlation between downstaging, survival and pre-treatment staging. MATERIAL AND METHODS: Between March 1995 and August 1998, 46 consecutive patients with pathology proven N2 disease were treated with three cycles of vindesine-ifosfamide-platinum (VIP). All patients underwent a rigorously performed cervical mediastinoscopy. Patients with at least partial response (n = 26) were surgically explored. RESULTS: The clinical response rate to chemotherapy was 57% (26 patients). Resection was complete in 23 patients (88.5%). Pneumonectomy was performed in 16 patients. In 11 patients (42.9%) the mediastinal nodes (which were positive at mediastinoscopy) had become negative (downstaging group). The projected 2-year survival of resected patients is 41%. Patients with downstaging of nodes had no better survival compared to patients with no downstaging. Patients with involved subcarinal nodes at mediastinoscopy and patients with involvement of more than one level had a worse survival. CONCLUSION: Surgery in N2-patients responsive to induction chemotherapy resulted in a high complete resectability rate. Findings at pre-treatment mediastinoscopy proved to be the most important prognostic factor.
The aim of primary surgery in the treatment of carcinoma of the esophagus and gastroesophageal junction (GEJ) is definite cure. To obtain this goal R0 resection, i.e. complete macroscopic and microscopic removal is of paramount importance. However, one of the most controversial questions remains the extent of lymph node dissection, in particular the value of cervical lymph node dissection (the so called third field). Three arguments are believed to favour more extended lymphadenectomy: optimal staging, prolonged tumour control, improved cure rate. (a) Optimal staging: available data indicate that unforeseen lymph node involvement in the neck is encountered in approximately 30% of the patients after 3-field lymphadenectomy. Even in tumours of the GEJ up to 20% of the patients in the T3N+ setting have unforeseen positive nodes in the neck. (b) Prolonged tumour control: radical esophagectomy and extensive lymphadenectomy is decreasing locoregional recurrence substantially, below 10%, in several published reports. More over extended lymphadenectomy seems to defer onset of locoregional recurrence and generalised metastasis for up to 3 years or more. (c) Improved cure rate: despite a lack of prospective randomised study many studies indicate a distinct survival benefit after radical esophagectomy and extensive lymphadenectomy. From the available data it becomes clear that radical surgery and extensive lymphadenectomy offers the best chances for prolonged survival or cure. This can be done without increasing hospital mortality and morbidity. Survival figures obtained by this technique are a gold standard to which survival obtained by other techniques (e.g. multimodality treatment forms, VATS resections) have to be compared.
Inhaled 5-hydroxytryptamine (5-HT) causes bronchoconstriction in asthmatics, and 5-HT plasma levels are elevated in asthma. Electrical field stimulation (EFS) of human airways, in vitro, evokes cholinergic contraction mediated by the release of acetylcholine (Ach) from postganglionic cholinergic nerves. The present study investigates whether selective 5-HT agonists and antagonists can modulate EFS-induced cholinergic contraction in human airways in vitro. Human airways, obtained from resections for bronchial carcinoma or organ transplant donors, were suspended under 2-g tension, between two platinum wire electrodes, in carbogenated Krebs solution at 37 degrees C and EFS was applied (1-32 Hz, 50 V, 0.5 ms, 15 s every 4 min) to elicit cholinergic contractions. 5-HT (10 microM-0.3 mM) produced frequency- and concentration-dependent facilitation of cholinergic contraction, but did not displace the concentration/response curve to Ach. Tropisetron (1 microM), a 5-HT3 and 5-HT4 antagonist, completely blocked the facilitatory effect of 5-HT (100 microM), whereas both ondansetron (1 microM) and GR 125478D (1 microM), a selective 5-HT3 and 5-HT4 antagonist, respectively, also attenuated the 5-HT-induced enhancement of cholinergic contraction. This facilitatory effect of 5-HT was partially mimicked by both selective 5-HT3 (2-methyl-5-HT) and 5-HT4 (RS 67333 and 5-methoxytryptamine) agonists. Fluoxetine (10 microM), a 5-HT uptake inhibitor, had no effect on the 5-HT (10-100 microm) induced potentiation of cholinergic contraction. These findings suggest that 5-HT facilitates cholinergic contraction in human airways in vitro through stimulation of both prejunctional 5-HT3 and 5-HT4 receptors. This may implicate a role of 5-HT in asthma.
Mucormycosis is a rare and invasive mycotic opportunistic infection, occurring mostly in predisposed patients, mainly diabetics and immunocompromised individuals. The evolution of this fungal infection is frequently fatal unless aggressive treatment is started, or predisposing factors are handled. Our first patient was a known diabetic who had ketoacidotic coma at admission, complicated with pulmonary mucormycosis, and needed surgical resection followed by antimycotic therapy. The second patient did not survive his severe aplastic anemia (with neutropenia) and hemochromatosis (treated with desferrioxamine), complicated with a systemic Rhizopus infection, despite treatment with amphotericin B and granulocyte-colony-stimulating factors.
Epinastine is an antihistamine drug with binding affinities at 5-hydroxytryptamine (5-HT) receptors. The current study was performed to investigate whether epinastine could modulate the cholinergic contraction in guinea pig and human airways in vitro. Isolated guinea pig and human airway preparations were suspended in organ baths containing modified Krebs-Henseleit solution. Electrical field stimulation was applied to elicit cholinergic contractions. Epinastine produced a concentration-dependent inhibition of the cholinergic contraction in guinea pig airways and pretreatment with methysergide (5-HT1/2/7 antagonist) significantly attenuated these inhibitory effects of epinastine. Pretreatment with tropisetron (5-HT3/4 antagonist), ketanserin (5-HT2 antagonist), SDZ216-525 (5-HT1A antagonist) or phentolamine (alpha-adrenergic antagonist) had no effect. Epinastine did not displace the concentration-response curve to acetylcholine. These results suggest that epinastine inhibits the cholinergic contraction in guinea pig airways through stimulation of prejunctional 5-hydroxytryptamine receptors, located to postganglionic cholinergic nerves. Inhibitory effects of epinastine on the cholinergic contraction in human airways in vitro were also demonstrated, which suggests that a similar mechanism might be present in human airways. The pharmacological profile of epinastine, which shows binding affinity at the 5-hydroxytryptamine7 receptor but not at the 5-hydroxytryptamine1 receptor subtypes corroborates the hypothesis that the inhibitory prejunctional 5-hydroxytryptamine receptor on cholinergic nerves is of the 5-hydroxytryptamine7 subtype.
Cancer of the esophagus and gastroesophageal junction remains a virulent malignancy with an overall poor prognosis. Especially in the Western hemisphere, the incidence of adenocarcinoma is sharply rising. Over the last two decades, surgery has become the mainstay of treatment. Decreased surgical mortality and standardization of oncologic principles focusing on the completeness of resection are believed to be responsible for the improved 5-year survival rates, which are reaching > or = 30%. Until now, there has been no proven benefit from combined neoadjuvant treatment modalities using chemotherapy or chemoradiotherapy except for the subset of patients showing a complete response at pathologic examination. Further research should focus on new chemotherapeutic agents and the development of molecular markers that allow better identification of candidates for multimodality regimens.
BACKGROUND: Surgical exploration in mediastinoscopy proven N2 non-small cell lung cancer (NSCLC) is unrewarding. Theoretical concepts suggest a beneficial role for preoperative induction treatment. The solidity of the therapeutic results with this approach in the currently available data is examined. METHODS: Literature on induction therapy followed by surgical exploration, consisting of randomized reports and phase II reports meeting some essential criteria, are reviewed. RESULTS: Of the twenty-four analyzed phase II studies, thirteen lack adequate surgical staging. Stratification for various important prognostic factors in N2 disease is missing in many instances. Results with induction with a cisplatinum dose of less than 80 mg/m2 seem to be inferior. The use of mitomycin-C in patients scheduled for lung resection or irradiation deserves caution. No evident difference in efficacy between induction chemotherapy or chemo-radiotherapy is suggested, but toxicity and mortality appear to be somewhat higher with chemo-radiotherapy. Pathological complete response is mainly found after an at least partial clinical response. Effect on survival in non-controlled phase II studies and small randomized reports is encouraging. CONCLUSIONS: the role of chemotherapy induction in improving the long-term survival of N2 NSCLC is promising, but needs to be confirmed by large multi-center randomized data. Adequate surgical staging and attention to important prognostic factors in N2 disease should minimize the numerous institution based differences interfering in the currently available non-controlled studies.
Electrical field stimulation of guinea pig tracheal strips and human bronchial rings, in vitro, evokes a cholinergic contraction mediated by the release of acetylcholine. 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) is a 5-HT1A and 5-HT7 agonist. In this study, we have investigated whether 8-OH-DPAT could modulate the cholinergic contraction in guinea pig and human airways in vitro. 8-OH-DPAT (1 to 30 microM) produced a concentration-dependent inhibition of the cholinergic contraction in guinea pig tracheal strips with a maximal inhibition of 75.8% +/- 4. 7% (30 microM, 0.5 Hz). Pretreatment of the tissues with the 5- HT1/2/7 antagonist methysergide (10 to 30 microM) significantly attenuated the inhibitory effects of 8-OH-DPAT (10 to 30 microM) on the cholinergic contraction. Pretreatment with ketanserin (10 microM), a 5-HT2 antagonist, tropisetron (1 microM), a 5-HT3/4 antagonist, SDZ 216-525 (1 to 10 microM) and pindobind (10 microM), both selective 5-HT1A antagonists, or capsaicin (10 microM), which depletes sensory nerves from neuropeptides, had no effect on the inhibition of the cholinergic contraction by 8-OH-DPAT (10 to 30 microM). 5-carboxamidotryptamine (5-CT) (10 to 100 microM), a 5-HT1/2/7 agonist, partially mimicked the inhibitory effects of 8-OH-DPAT on the cholinergic contraction. 8-OH-DPAT (10 to 30 microM) also inhibited the cholinergic contraction in human bronchial rings in vitro with a maximal inhibition of 46.2% +/- 7.2% (30 microM, 1 Hz). SDZ 216-525 (10 microM) had no effect, whereas methysergide (30 microM) partially prevented the effect of 8-OH-DPAT in human airways. 8-OH-DPAT (30 microM) did not displace the concentration-response curve to acetylcholine (10 nM-30 mM) in guinea pig and human airways in vitro. These results suggest that 8-OH-DPAT inhibits the cholinergic contraction in guinea pig and human airways in vitro through stimulation of prejunctional atypical 5-HT receptors, possibly of the 5-HT7 subtype, located on postganglionic cholinergic nerves.
Heparan sulfate (HS) functions as a co-factor in several signal-transduction systems that affect cellular growth, differentiation, adhesion and motility. HS, therefore, may also play a role in the malignant transformation of cells, tumor growth, cell invasiveness and the formation of tumor metastases. To explore this hypothesis, we analyzed the expression of HS and heparan sulfate proteoglycan (HSPG) in histological sections of human lung-cancer tissues and assayed for the presence of HSPGs in extracts of human lung-cancer cell lines, using a panel of native HS-, delta-HS- and HSPG (syndecan, glypican, CD44 and perlecan) core protein-specific monoclonal antibodies. Compared to normal epithelia, non-small-cell lung carcinomas, particularly poorly differentiated tumors, often expressed reduced amounts of the major cell surface-associated HSPGs (most consistently of syndecan-1). CD44 or CD44-variant proteins, in contrast, were found on all tumor cells, irrespective of their differentiation. Perlecan, a matrix-associated HSPG found in the basement membrane of normal bronchial epithelium, was consistently undetectable in invasive bronchogenic carcinomas. Staining reactions for native HS were consistently reduced in squamous-cell lung carcinomas, in the cells in contact with the stroma and in the less differentiated areas of these tumors. Reactions for delta-HS, however, were not reduced, suggesting a structural change in the HS of these tumor cells. Poorly differentiated adenocarcinomas, in contrast, yielded strong HS and delta-HS reactions. Marked differences in HSPG expression also were observed among various non-small-cell lung carcinoma cell lines. Our results suggest that poorly differentiated lung tumors have markedly altered patterns of HSPG expression, which may contribute to their invasive phenotype.
The endoscopic approach to adrenal glands has been limited to laparoscopic and retroperitoneal access due to the relative inaccessibility of the retroperitoneal space in the former case and to the limited working space in the latter. We undertook this study to investigate the possibility of performing a left adrenalectomy through a thoracoscopic transdiaphragmatic approach in a swine model. Five pigs were anesthetized, intubated, and ventilated. Four laparoscopic trocars were inserted and a left pneumothorax was accomplished by CO2 insufflation. A peripheral posterior phrenotomy was made starting from the aortic hiatus and extended laterally for about 6 cm. The resulting pneumoretroperitoneum facilitated the subsequent identification of anatomic structures, allowing an easy exposure of the left adrenal gland. The gland was progressively dissected downward, interrupting the tributary vessels with endoscopic clips, and it was finally extracted through one of the trocar ports. Adrenalectomy was accomplished in all the animals without intraoperative mortality. Complications included splenic injury with prolonged bleeding and difficulty in performing the diaphragmatic suture (one case each). Through this approach direct and rapid exposure of the left adrenal gland was allowed, and adrenalectomy was accomplished in all the animals. These results suggest further investigations of the clinical application of this procedure.
OBJECTIVE: Minimal invasive antireflux surgery is now a well accepted technique gaining a wide spread popularity. Simultaneously there is a growing tendency to fit all surgical candidates into one single type of operation, i.e. laparoscopic Nissen antireflux operation. This study evaluates the impact of this new technology on the strategy and practice of a major referral centre for antireflux surgery. METHODS: An analysis was made of indications for the different types of antireflux techniques performed between July, 1993 and 1995. If on Barium swallow the gastro-oesophageal (GO) junction proved to be reducible, a laparoscopic approach was proposed, if not, an open transthoracic access was preferred. RESULTS: One hundred and fifteen patients were operated. Fifty five patients underwent a minimal invasive approach: 49 Nissen (are the total fundoplication) and 3 Lind (are the partial fundoplication) operations through laparoscopy, 3 Belsey Mark IV through video assisted thoracic surgery (VATS). Sixty patients were treated by open surgery for following reasons: conversion to open surgery in 2 cases, redo surgery in 15 cases, previous other major abdominal surgery in 12, irreducible GO junction in 5, paraoesophageal or mixed type hernia in 12, Barrett and or oesophagitis IV in 4, combined antireflux surgery and feeding gastrostomy in 5, abdominal partial fundoplication by principle in 1, associated motility disorder in 1, combined reflux and gastric ulcer disease in 2, and severe emphysema in 1. In the laparoscopic series reflux control at 1 year post surgery as measured by 24 h pH study in 28 patients was obtained in 89.5%. One patient required a reoperation for symptomatic recurrence. CONCLUSIONS: (1) Laparoscopic antireflux surgery is a feasible and well accepted technique; (2) careful study of each individual patient is of paramount importance to choose the correct type of operation and access as well. Therefore, fitting every patient into a single type of operation, i.e. laparoscopic Nissen, should be avoided; (3) thoracic surgeons with a major interest in GO reflux disease should familiarize themselves with laparoscopic antireflux procedures.
OBJECTIVE: The results of primary surgery for non-small cell lung cancer (NSCLC) with involved ipsilateral mediastinal or subcarinal lymph nodes (N2 disease) remains poor. However, several studies suggest that induction chemotherapy could increase long-term survival in patients with N2 disease. Therefore, accurate preoperative staging of the mediastinum remains of paramount importance for the treatment policy in patients with NSCLC. Enlarged mediastinal lymph nodes (MLN) on CT scan are positive in only half of the patients. Small lymph nodes can contain metastatic deposits of clinical importance. However, many surgeons believe that a normal mediastinum at computed tomography allows them to cancel their preoperative mediastinal exploration. It was the aim of this study to evaluate the results of cervical mediastinoscopy in patients without enlarged MLN on CT scan. METHODS: Between January 1990 and June 1994, 235 patients with potentially operable NSCLC underwent a cervical mediastinoscopy despite the absence of enlarged MLN on CT scan. MLN were considered enlarged if they were equal to or larger than 15 mm at their maximal cross-sectional diameter. RESULTS: Cervical mediastinoscopy was positive in 47 patients (20%). In 21 patients, N2 disease was extranodal and in 16 patients more than one level was involved. Mediastinoscopy was positive in 9.5% of the cT1N0 cases, in 17.7% of the cT2N0 lesions, in 31.2 and 33.3% of cT3N0 or cT4N0 tumors, respectively. After a negative cervical mediastinoscopy, resectability for unforeseen N2 disease was as high as 95%. CONCLUSION: We recommend a cervical mediastinoscopy in every patient with potentially operable NSCLC.
Cytogenetic analysis of a thymoma revealed the presence of a t(15;22)(p11;q11) as the only chromosome abnormality. From the few thymomas so far analyzed, no characteristic chromosome change seems to be emerging.